Henze D A, González-Burgos G R, Urban N N, Lewis D A, Barrionuevo G
Department of Neuroscience, Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Neurophysiol. 2000 Dec;84(6):2799-809. doi: 10.1152/jn.2000.84.6.2799.
Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 (n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 microM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 microM) but not significantly altered by the D2 antagonist sulpiride (2.5 microM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.
多巴胺能对背外侧前额叶皮质（PFC）神经网络的调节，被认为在人类和非人类灵长类动物执行工作记忆任务期间的信息处理中发挥重要作用。为了理解多巴胺（DA）这些作用背后的基本细胞机制，我们研究了DA对猕猴PFC 46区第3层锥体细胞的细胞特性的影响。在PFC脑片标本中，使用尖锐电极和全细胞膜片钳电极进行细胞内电压记录。第3层中所有记录的神经元（n = 86）均表现出与锥体细胞一致的规则放电特性。我们发现，DA对这些细胞的静息膜电位或输入电阻没有显著影响。然而，低至0.5微摩尔浓度的DA，会增加PFC细胞对注入胞体的去极化电流阶跃的兴奋性。兴奋性增强与动作电位阈值的超极化偏移和首次峰峰间期缩短有关。这些效应需要激活D1样受体而非D2样受体，因为它们被D1受体拮抗剂SCH23390（3微摩尔）抑制，但未被D2拮抗剂舒必利（2.5微摩尔）显著改变。这些结果首次表明，DA在体外调节猕猴背外侧PFC 46区第3层锥体细胞的活性。此外，这些结果表明，仅通过这些效应，DA调节通常会增强PFC锥体细胞对到达动作电位起始位点的兴奋性电流的反应。
